| Identification | More | [Name]
Niclosamide | [CAS]
50-65-7 | [Synonyms]
2',5-DICHLORO-4'-NITROSALICYLANILIDE
2',5-DICHLORO-4-NITROSALICYLANILIDE
2-CHLORO-4-NITROPHENYLAMIDE-6-CHLOROSALICYLIC ACID
2-hydroxy-5-chloro-n-(2-chloro-4-nitrophenyl)benzamide
5-chloro-2'-chloro-4'-nitrosalicylanilide
5-CHLORO-N-(2-CHLORO-4-NITROPHENYL)-2-HYDROXYBENZAMIDE
5-CHLORO-N-(2-CHLORO-4-NITROPHENYL)-SALICYLAMIDE
bayluscid
BAYLUSCIDE
BAYLUSCIDE(R)
MANSONIL(R)
NICLOSAMID
NICLOSAMIDE
YOMESAN
YOMESAN(R)
2’,5-dichlor-4’-nitro-salizylsaeureanilid
2’,5-dichlor-4’-nitro-salizylsaeureanilid[german]
2’,5-dichloro-4’-nitro-salicylanilid
5-chloro-n-(2-chloro-4-nitrophenyl)-2-hydroxy-benzamid
5-chlorosalicyloyl-(o-chloro-p-nitranilide) | [EINECS(EC#)]
200-056-8 | [Molecular Formula]
C13H8Cl2N2O4 | [MDL Number]
MFCD00057597 | [Molecular Weight]
327.12 | [MOL File]
50-65-7.mol |
| Chemical Properties | Back Directory | [Appearance]
Yellowish-white or yellowish, fine crystals. | [Melting point ]
225-230° | [Boiling point ]
424.5±45.0 °C(Predicted) | [density ]
1.6646 (rough estimate) | [refractive index ]
1.6200 (estimate) | [storage temp. ]
0-6°C | [solubility ]
acetone: methanol: soluble50mg/mL (methanol:acetone (1:1)) | [form ]
Pale yellow solid | [pka]
7.45±0.43(Predicted) | [color ]
Yellow | [Water Solubility ]
13.32mg/L(25 ºC) | [BRN ]
2820605 | [BCS Class]
4 | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. | [InChIKey]
RJMUSRYZPJIFPJ-UHFFFAOYSA-N | [Uses]
Niclosamide has been used extensively in the treatment of tapeworm infections caused by Taenia saginata, Taenia solium, Diphyllobothrium latum, Fasciolopsis buski, and Hymenolepis nana. It is an effective alternative to praziquantel for treating infections caused by T. saginata (beef tapeworm), T. solium (pork tapeworm), and D. latum (fish tapeworm) and is active against most other tapeworm infections. It is absorbed by intestinal cestodes but not nematodes.A single dose is usually adequate to produce a cure rate of 95%.With H. nana (dwarf tapeworm), a longer treatment course (up to 7 days) is necessary. Niclosamide is administered orally after the patient has fasted overnight and may be followed in 2 hours by purging (magnesium sulfate 15–30 g) to encourage complete expulsion of the cestode, especially T. solium, although this is not always considered necessary. Cure is assessed by follow-up stool examination in 3 to 5 months.With the availability of other agents, niclosamide is no longer widely used.The most widely employed agents are praziquantel and the benzimidazoles. | [CAS DataBase Reference]
50-65-7(CAS DataBase Reference) | [EPA Substance Registry System]
50-65-7(EPA Substance) |
| Safety Data | Back Directory | [Risk Statements ]
50 | [Safety Statements ]
29 | [RIDADR ]
UN 3077 9/PG 3
| [WGK Germany ]
2
| [RTECS ]
VN8400000
| [HS Code ]
29242990 | [Safety Profile]
Poison by intravenous
and intraperitoneal routes. Moderately toxic
by ingestion. Experimental reproductive
effects. Human mutation data reported.
When heated to decomposition it emits very
toxic fumes of Cl and NOx. | [Hazardous Substances Data]
50-65-7(Hazardous Substances Data) | [Toxicity]
LD50 oral in rat: 2500mg/kg |
| Hazard Information | Back Directory | [Description]
Niclosamide (50-65-7) reversibly inhibits mTORC1 signaling and stimulates autophagy.1 Inhibits activation and nuclear translocation of STAT3 selectively over STAT1 and STAT5. Niclosamide inhibits transcription of STAT3 target genes and induces cell cycle arrest and apoptosis in cells with constitutively active STAT3.2 | [Chemical Properties]
Yellowish-white or yellowish, fine crystals.Yellow-white crystalline powder, odorless, tasteless. Melting point 225-230 ℃. Insoluble in water, soluble in hot ethanol, chloroform, cyclohexanone, diethyl ether and sodium hydroxide solution.
| [Originator]
Yomesan,Bayer,W. Germany,1960 | [Definition]
ChEBI: Niclosamide is a secondary carboxamide resulting from the formal condensation of the carboxy group of 5-chlorosalicylic acid with the amino group of 2-chloro-4-nitroaniline. It is an oral anthelmintic drug approved for use against tapeworm infections. It has a role as a piscicide, a molluscicide, an antiparasitic agent, an anticoronaviral agent, an anthelminthic drug, an apoptosis inducer and a STAT3 inhibitor. It is a member of monochlorobenzenes, a member of salicylanilides, a C-nitro compound, a secondary carboxamide and a member of benzamides. It is functionally related to a 5-chlorosalicylic acid. | [Manufacturing Process]
17.2 g of 5-chlorosalicylic acid and 20.8 g of 2-chloro-4-nitroaniline are
dissolved in 250 ml of xylene. While boiling, there are introduced slowly 5 g of
PCl3.Heating is continued for 3 further hours. The mixture is then allowed to
cool down and the crystals which separate are filtered off with suction. The
crude product may be recrystallized from ethanol, melting at 233°C. | [Brand name]
Niclocide (Bayer). | [Therapeutic Function]
Anthelmintic | [Antimicrobial activity]
Useful activity is restricted to intestinal tapeworms, including Taeniarhynchus saginatus (syn. Taenia saginata), Taenia solium, Diphyllobothrium latum and Hymenolepis nana. It is not effective against larval stages of tapeworms. | [General Description]
A cell-permeable salicylanilide that, in addition to its well-known antihelmintic efficacy, acts as a mammalian mTORC1, but not mTORC2, signaling inhibitor mechanistically distinct from rapamycin. Likely a direct consequence of autophagy activation, Niclosamide is demonstrated to induce Wnt-independent Frizzled1 and Dishevelled-2 downregulation. Unrelated to its autophagy induction activity, Niclosamide is also shown to inhibit Stat3 signaling (IC50 = 0.25 M in HeLa reporter assays). Efficiently inhibits breast cancer stem-like cells in vitro and in vivo. | [Pharmaceutical Applications]
A synthetic chlorinated nitrosalicylanilide available for oral
administration. | [Biochem/physiol Actions]
Niclosamide uncouples oxidative phosphorylation in the tapeworm and inhibits mitochondrial oxidative phosphorylation of parasitic helminths. It blocks tumor necrosis factor-induced IκBα phosphorylation, translocation of p65, and expression of NF-κΒ– regulated genes in AML cells. | [Mechanism of action]
For many years, niclosamide (Niclocide) was widely used to treat infestations of cestodes. Niclosamide is a chlorinated salicylamide that inhibits the production of energy derived from anaerobic metabolism. It may also have adenosine triphosphatase (ATPase) stimulating properties. Inhibition of anaerobic incorporation of inorganic phosphate into ATP is detrimental to the parasite. Niclosamide can uncouple oxidative phosphorylation in mammalian mitochondria, but this action requires dosages that are higher than those commonly used in treating worm infections.
The drug affects the scolex and proximal segments of the cestodes, resulting in detachment of the scolex from the intestinal wall and eventual evacuation of the cestodes from the intestine by the normal peristaltic action of the host's bowel. Because niclosamide is not absorbed from the intestinal tract, high concentrations can be achieved in the intestinal lumen.The drug is not ovicidal. | [Mechanism of action]
For many years, niclosamide (Niclocide) was widely
used to treat infestations of cestodes. Niclosamide is a
chlorinated salicylamide that inhibits the production of
energy derived from anaerobic metabolism. It may also
have adenosine triphosphatase (ATPase) stimulating
properties. Inhibition of anaerobic incorporation of inorganic
phosphate into ATP is detrimental to the parasite.
Niclosamide can uncouple oxidative phosphorylation
in mammalian mitochondria, but this action
requires dosages that are higher than those commonly
used in treating worm infections.
The drug affects the scolex and proximal segments of
the cestodes, resulting in detachment of the scolex from
the intestinal wall and eventual evacuation of the cestodes
from the intestine by the normal peristaltic action
of the host’s bowel. Because niclosamide is not absorbed
from the intestinal tract, high concentrations can be
achieved in the intestinal lumen.The drug is not ovicidal. | [Pharmacokinetics]
Conflicting data exist relative to the level of absorption of
niclosamide from the gut. The metabolized drug is passed in
the feces and urine, staining them yellow. | [Clinical Use]
5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamideor 2,5 -dichloro-4 -nitrosalicylanilide (Cestocide, Mansonil,Yomesan) occurs as a yellowish white, water-insolublepowder. It is a potent taeniacide that causes rapid disintegrationof worm segments and the scolex. Penetration of thedrug into various cestodes appears to be facilitated by thedigestive juices of the host, in that very little of the drug isabsorbed by the worms in vitro. Niclosamide is well toleratedfollowing oral administration, and little or no systemicabsorption of it occurs. A saline purge 1 to 2 hours after ingestion of the taeniacide is recommended to remove thedamaged scolex and worm segments. This procedure ismandatory in the treatment of pork tapeworm infestation toprevent possible cysticercosis resulting from release of liveova from worm segments damaged by the drug. | [Clinical Use]
Intestinal tapeworm infections | [Clinical Use]
Niclosamide has been used extensively in the treatment
of tapeworm infections caused by Taenia saginata, Taenia
solium, Diphyllobothrium latum, Fasciolopsis buski, and
Hymenolepis nana. It is an effective alternative to praziquantel
for treating infections caused by T. saginata (beef
tapeworm), T. solium (pork tapeworm), and D. latum
(fish tapeworm) and is active against most other tapeworm
infections. It is absorbed by intestinal cestodes but
not nematodes.A single dose is usually adequate to produce
a cure rate of 95%.With H. nana (dwarf tapeworm),
a longer treatment course (up to 7 days) is necessary.
Niclosamide is administered orally after the patient has
fasted overnight and may be followed in 2 hours by purging
(magnesium sulfate 15–30 g) to encourage complete
expulsion of the cestode, especially T. solium, although
this is not always considered necessary. Cure is assessed
by follow-up stool examination in 3 to 5 months.With the
availability of other agents, niclosamide is no longer
widely used.The most widely employed agents are praziquantel
and the benzimidazoles. | [Synthesis]
Niclosamide, 2,5-dichloro-4nitrosaicylanilide (38.1.34), is made by reacting 5-chlorosalicylic acid with 2-chloro-4-nitroaniline in the presence of phosphorus trichloride.
| [storage]
+4°C |
| Questions And Answer | Back Directory | [Anti-parasitic disease drug]
Niclosamide belongs to the taeniafuge drugs of the anti-parasitic disease drugs , it is less toxic, it has a high efficacy on a variety of tapeworm, tapeworm mechanism is hampering tapeworm Krebs cycle, so that lactic acid is accumulated which can cause the death of the parasites, it is drug of choice in livestock and poultry, pet tapeworm prevention . Oral absorption from the gastrointestinal tract is very little, so it can maintain a high concentration in the intestine, it has a strong insecticidal action against the pork tapeworm, and beef tapeworm short Hymenolepis . Low concentrations of the drug can promote parasite uptake, while high concentrations of the drug can inhibit mitochondrial oxidative phosphorylation of the parasite, and hinder the absorption of glucose uptake,and result in tapeworm head and proximal segments death, and elimination with the feces from the intestinal wall . Mainly it is used for tapeworm infection, but it is also used as molluscidal drugs which can kill snails and snail eggs, cercariae and miracidia. It has high rate of snail eradication , slow effect, long residual effect, it is used for the prevention of schistosomiasis, the temperature above 20 ℃ is better. In addition ,the product is friendly to human, animal and plant,it is very toxic to fish, so use in the fish ponds is forbidden .
1960 Germany reported a synthetic chemical repellent-Niclosamide whose code is Bayer 73 the drug is pale yellow powder, odorless, tasteless. Insoluble in water, slightly soluble in alcohol, ether and chloroform,it can be dissolved in hot ethanol, cyclohexanone and an aqueous solution of sodium hydroxide, the compound is stable.Niclosamide have a better effect on beef tapeworm, pork tapeworm, H. nana and Diphyllobothrium tapeworm, . Few drug absorption occurs in the gastrointestinal tract, when the drug is exposed with parasites, parasites die soon. Therefore, when the medication, the tablets should be chewed, so drugs can make full contact with tapeworm parasites, and a lot of water immediately should be avoided, in order to maintain a high concentration of upper small intestine where lies the parasitic tapeworm . The drug can kill adults tapeworm rather than eggs tapeworm , in order to prevent vomiting, which make the eggs reflux into stomach , and cause the risk of cysticercosis occurring, anti-emetics should be added before the medication . 2 hours after administration, it should be served magnesium sulfate for catharsis, to get rid of the parasite and the cleaved head section and debris. The drug has low toxicity, rat oral LD50 of 5g/kg. This product can also be made with amino ethanol to serve as soluble snail drugs under the trade name niclosamide (bayluscide),in the country, Niclosamide and alkali waste pulp can be made for soluble pastes, called schistosomiasis-67. These can be used to kill the snail which is the intermediate host of Schistosoma japonicum. Regardless of spraying or soaking ,the amount of snail, is 1g/m2. Pulp paste for live use (ie schistosomiasis-67), accounts for 50% of Niclosamide . Oral adverse reactions are mild, except for gastrointestinal reactions, occasional dizziness, chest tightness, fever and other discomfort occur. There is no liver, kidney, blood system injury.
The above information is edited by the chemicalbook of Tian Ye. | [Pharmacology and mechanism of action]
Niclosamide is a chlorinated salicylanilide derivative which was introduced during the 1960s. It is an anthelminthic drug highly effective against beef tapeworm (Taenia (T.) saginata), pork tapeworm (T. solium), fish tapeworm (Diphyllobothrium (D.) latum) and dwarf tapeworm (Hymenolepis (H.) nana).
The mechanism of action of the drug is not clearly known. It interferes with the energy metabolism of helminths, possibly by inhibiting adenosine triphosphate (ATP) production. It also inhibits glucose uptake by the parasites [1].
| [Indications]
Infections caused by T. saginata, D. latum, and H. nana. The drug is also effective against T. solium, but the danger of cysticercosis makes praziquantel preferable.
| [Contraindications and precautions]
Drugs which cause vomiting should not be taken simultaneously with niclosamide to avoid retrograde infection by eggs. Use of niclosamide against T. solium infection may expose the patient to the risk of cysticercosis. In such a case, special precautions are needed (see Dosage below).
| [Side effects]
Niclosamide is generally free of undesirable effects. Minor gastrointestinal complaints such as nausea, vomiting, abdominal pain, diarrhoea, light-headedness and pruritus are rarely encountered.
| [Preparations]
• Niclocide® (Miles). Tablets 500 mg.
• Trédémine® (Bellon). Tablets 500 mg.
• Yomesan® (Bayer). Tablets 500 mg.
| [Acute toxicity]
Oral-rat LD50: 2500 mg/kg; Oral-Mouse LD50: 1000 mg/kg
| [Flammability and hazard characteristics]
It produces toxic chloride and nitrogen oxide gases from combustion.
| [Storage Characteristics]
Ventilated, low-temperature ,dry storeroom.It should be stored and transported separately
From food raw materials
| [Extinguishing agent]
Dry powder , foam, sand
| [References]
1. Webster LT Jr (1990). Drugs used in the chemotherapy of helminthiasis. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 8th edn, edited by A.G.Gilman, T.W.Rall, A.S.Nies, P.Taylor, (New York: Pergamon Press), pp. 965–966.
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